期刊
DEVELOPMENTAL CELL
卷 41, 期 4, 页码 392-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2017.04.024
关键词
-
资金
- NIH Office of Research Infrastructure Programs [P40 OD010440]
- Nucleic Acid Core Shared Resources at Ohio State University
- Breast Cancer Functional Genomics Group at McGill University
- NIH [P01 CA097189]
- Pelotonia Fellowships
- NIH T32 fellowship [5 T32 CA106196-9]
- [NSF IOB-0949489]
- [NSF/NIH DMS-1361251]
- Division Of Mathematical Sciences
- Direct For Mathematical & Physical Scien [1361251] Funding Source: National Science Foundation
Mesodermal cells signal to neighboring epithelial cells to modulate their proliferation in both normal and disease states. We adapted a Caenorhabditis elegans organogenesis model to enable a genome-wide mesodermal-specific RNAi screen and discovered 39 factors in mesodermal cells that suppress the proliferation of adjacent Ras pathway-sensitized epithelial cells. These candidates encode components of protein complexes and signaling pathways that converge on the control of chromatin dynamics, cytoplasmic polyadenylation, and translation. Stromal fibroblast-specific deletion of mouse orthologs of several candidates resulted in the hyper-proliferation of mammary gland epithelium. Furthermore, a 33-gene signature of human orthologs was selectively enriched in the tumor stroma of breast cancer patients, and depletion of these factors from normal human breast fibroblasts increased proliferation of co-cultured breast cancer cells. This cross-species approach identified unanticipated regulatory networks in mesodermal cells with growth-suppressive function, exposing the conserved and selective nature of mesodermal-epithelial communication in development and cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据